The invention relates to tetravalent bispecific receptors which are prepared by genetic manipulation by fusion of the DNA which codes for the heavy chain of an F(ab')2 fragment of an antibody (I) with (a) DNA which codes for the heavy chain of an F(ab')2 molecule of a second antibody (II), in which the CH1 domain is replaced by a CH3 domain (formula I), or with (b) the DNA which codes for a single chain FV fragment of an antibody (II) (formula II), by means of suitable linkers. The expression of these fusion genes in mammalian cells together with the genes for the corresponding light chains, which in the case of the construct (a) are composed on the one hand of a VL exon of specificity I and a CK exon, and on the other hand of a VL exon of specificity II and a CH3 exon, and in the case of the construct (b) only of a VL exon of specificity I and a CK exon, yields tetravalent bispecific receptors. In this case the CH1 domains are connected to the VH2 domains via 1 to 10 hinge regions (H) and a suitable peptide linker L. The antibody specificities described in European Patent Application EP-A2-0404 097 are preferably employed. They are, inter alia, on the one hand specificities which are directed against an epitope, which is located on the cell membrane or in the interstitium of a tumor-associated antigen. On the other hand, these are specificities which are directed against high or low molecular weight ligands which in turn bind an agent which is active against tumors, or bind this active agent directly.
EP-A2-0404 097 describes bispecific and oligospecific, mono- and oligovalent receptors which are prepared by genetic manipulation by fusion of DNA coding for F(ab) fragments of antibodies of two or more different specificities by means of suitable linkers. In this case, one specificity is; preferably directed either against an epitope, which, is located on the cell membrane or in the interstitium, of a tumor-associated antigen (TAA) or against an epitope in the tumor endothelium (TE), while the other specificities relate to high or low molecular weight ligands and react, for example, with the complexons ethylenediaminetetraacetate and diethylenetriaminepentaacetate in yttrium-90-complexed form (EDTA-90Y and DTPA-90Y respectively). In a particularly preferred embodiment, the binding to the complexons takes place on the complexon receptor arm via fos-jun interaction (or else avidin-biotin interaction). Other preferred specificities have catalytic properties.